Drugs and the cardiovascular system: the heart

Question 1

What is the primary controller of HR?

Answer 1

pacemaker cells in SA node.

Question 2

What ion channels are important to SA node action potential generation?

Answer 2

If- hyperpolarization-activated cyclic nucleotide–gated (HCN) channels

Ica (T or L) – Transient T-type Ca++channel or Long Lasting L-type Ca++channel

IK – Potassium K+channels

Question 3

Graph showing SA node action potential.

When are I_f I_ca and I_k channels active?

Answer 3

Question 4

What happens in phase 4 of the SA node action potential?

Answer 4

spontaneous depolarization –> action potential generation.

Question 5

What effects do increased SNS and PSNS innervation have on heart rate and through mediation of what factors?

Answer 5

Sympathetic - ↑cAMP, ↑ If & Ica

Parasympathetic - ↓ cAMP, ↑ IK

Question 6

Diagram to show how Ca2+ influx leads to cardiac muscle contraction.

Answer 6

Question 7

How is FOC controlled?

Answer 7

size of Ca2+ influx from SR and outside the cell.

Question 8

What factors lead to increased myocardial oxygen demand?

Answer 8

Increased:

HR

Preload

Afterload

Contractility.

Question 9

How is myocardial oxygen supply increased?

Answer 9

increased coronary blood flow and arterial O2 content.

Question 10

What drug categories are used to decrease HR?

What ion channel currents in the SA node do these drugs affect?

Answer 10

β-blockers – Decrease If and Ica

Calcium antagonists – Decrease Ica

Also Ivabradine– Decrease If

Question 11

How can myocardial contractility be controlled with drugs?

Answer 11

β-blockers – Decrease contractility

Calcium antagonists – Decrease Ica

Question 12

What are the two classes of Calcium antagonists?

What muscles do these classes effect?

Answer 12

Rate slowing (Cardiac and smooth muscle)

Phenylalkylamines(e.g. Verapamil)

Benzothiazepines(e.g. Diltiazem)

Non-rate slowing (smooth muscle only but more potent)

Dihydropyridines(e.g. amlodipine

(no effect on heart. Can –> reflex tachycardia)

Question 13

How can NO (and other organic nitrates) reduce contractility?

Answer 13

Promotes opening of potassium channel opening (–> hyperpolarisation, so contraction is more difficult)

increase GTP –> cGMP via sGC which promotes cellular relaxation.

Question 14

How do NO and potassium channel openers effect preoload and afterload?

Answer 14

Vasodilation = ↓ afterload

Venodilation= ↓ preload

Question 15

Why is heart failure contraindicated against beta blocker administration?

Answer 15

Reduced cardiac output

Increased vascular resistance

Question 16

Why is bardycardia contraindicated against beta blocker administration?

Answer 16

Heart block – decreased conduction through AV node.

HR reduced even further.

Question 17

What problems arise with pindolol administration?

Answer 17

Some intrinsic sympathetic activity so effects might only kick in during exercise

Question 18

Why are beta blockers contraindicated against diabetes?

Answer 18

SNS activity leads to gluconeogenesis - blocking receptors in liver prevents this –> hypo

Question 19

Why might beta blocker administration lead to cold extremeties?

Answer 19

Loss of B2 receptor mediated vasodilation in extremeties - blood supply reduced.

Question 20

What are the potential side effects of verapamil?

Answer 20

Bradycardia and AV block (Ca2+ channel block)

Constipation (Gut Ca2+ channels)

Question 21

What are the common side effects of dihydropyridine administration?

Answer 21

Ankle oedema (increased vasodilation –> more pressure in capillary vessels)

Headache/flushing (vasodilation)

Palpitations (vasodilation –> reflex adrenergic activation)

Question 22

Why can arrhythmias lead to stroke?

Answer 22

Irregular heart beat –> less consistent blood flow –> easier clotting

Question 23

How are arrhythmias classified?

Answer 23

supraventricular and ventricular

complex (supraventricular + ventricular arrhythmias)

Question 24

What are the 4 categories of anti-arrhythmic drugs according to the Vaughan Williams classification?

Answer 24

1. Na clannel blockers
2. beta adrenergic blockade
3. Prolongation of repolarisation
4. Ca2+ channel blocker

Question 25

Explain adenosine’s anti-arrhythmic effects.

Answer 25

Bind to adenosine type 2A receptors –> reduced cAMP (in SA/AV nodes) –> recued chronotropy and dromotropy.

Attempts to restore normal rhythm by increasing time between aciton potentials.

Question 26

Explain the anti-arrhythmic action of verapamil.

Answer 26

Depress SA automaticity, increasing time between action potentials, attempting to increase regularity and distinction of contractions.

Question 27

What is amiodarone used for? Explain its mechanism of action.

Answer 27

treat both superventricular and ventricular tachyarrhythmias (often due to reentry).

K+ channel blockade - increase of repolarisation phase length so allowing cardiac relaxation.